Research Nodular melanoma is less likely than superficial spreading melanoma to be histologically associated with a naevus Yan Pan*,1,2, Nikki R Adler*,1,2, Rory Wolfe2, Catriona A McLean3, John W Kelly1 Abstract The known Primary cutaneous melanomas may arise de novo Objectives: To determine the frequency of naevus-associated or in association with a pre-existing naevus. Understanding the melanoma among superficial spreading and nodular subtypes; fi initial presentation of super cial spreading and nodular and to investigate associations between naevus-associated melanoma subtypes is vital for facilitating their early detection. melanoma and other clinico-pathological characteristics. The new Most melanomas develop without a pre-existing Design, setting and participants: Cross-sectional study of all naevus, particularly nodular melanomas, melanomas in patients with nodular and superficial spreading melanomas patients over 70 years of age, and amelanotic/hypomelanotic diagnosed between 1994 and 2015 at the Victorian Melanoma melanomas. Service, Melbourne. The implications It is important for public health campaigns Methods and main outcome measures: Clinical and to emphasise the importance of detecting suspicious de novo pathological characteristics of naevus-associated and de novo lesions, as well as changing lesions. melanomas were assessed in univariable and multivariable logistic regression analyses. Results: Of 3678 primary melanomas, 1360 (37.0%) were histologically associated with a naevus and 2318 (63.0%) were lthough only 10e15% of all invasive melanomas are de novo melanomas; 71 of 621 nodular (11.4%) and 1289 of 3057 nodular melanomas, this subtype is the predominant superficial spreading melanomas (42.2%) were histologically Acontributor to melanoma-related deaths.1 Nodular associated with a naevus. In multivariable analyses, the odds of melanomas often elude early detection and account for a being associated with a naevus were higher for melanomas located on the trunk (v head and neck: adjusted odds ratio [OR], disproportionately high number of thick primary melanomas, e P 1-3 2.27; 95% CI, 1.73 2.96; < 0.001), while the odds were lower partly because of their atypical clinical presentation (Box 1). for thicker tumours (adjusted OR, 0.75 per millimetre increase fi Super cial spreading melanoma is the most common in Breslow thickness; 95% CI, 0.69e0.81; P < 0.001), melanoma subtype, accounting for 55e65% of all melanomas amelanotic/hypomelanotic melanomas (adjusted OR, 0.68; 1 (Box 2). 95% CI, 0.48e0.97; P ¼ 0.035), and older age (patients 70 years or older v patients under 30 at diagnosis: adjusted OR, 0.28; Nodular melanomas often do not conform to the classical ABCDE 95% CI, 0.20e0.40; P < 0.001). After adjusting for confounders, criteria used to alert doctors and patients to the possibility of su- the odds of an associated naevus was three times as high for 1,3,4 perficial spreading melanoma. In contrast to superficial superficial spreading melanomas as for nodular melanomas spreading melanoma, characterised by a radial growth phase fol- (adjusted OR, 3.05; 95% CI, 2.24e4.17; P < 0.001). lowed by invasion into the dermis, nodular melanoma is charac- Conclusion: Melanomas are most likely to arise in the absence terised by early vertical growth. Nodular melanoma is also of a pre-existing naevus, particularly nodular melanomas. Public 5 associated with more rapid vertical growth, so that improving health campaigns should therefore emphasise the detection of diagnostic accuracy of nodular melanoma is crucial.1 Under- suspicious de novo lesions, as well as of changing lesions. standing the initial presentation of both these melanoma subtypes is vital for their early detection. reported that nodular melanomas typically arise de novo and are Primary cutaneous melanomas may arise de novo or in associ- only infrequently associated with a contiguous naevus.6,12,15 The ation with a pre-existing naevus. Based on histological assess- aim of our study was to determine the frequency of naevus- ment, naevus-associated melanomas are estimated to represent associated melanoma among superficial spreading and nodular 19e58% of all cutaneous melanomas.6-17 A clinical history of melanoma subtypes, which together account for about 70% of a longstanding precursor pigmented lesion is reported by invasive melanomas and are the most common radial and ver- patients for 40e45% of all biopsy-proven melanomas.11 tical growth phase melanoma subtypes. Accurately under- MJA 207 (8) However, a reported precursor pigmented lesion may be a standing how often superficial spreading and nodular melanoma slowly progressing early melanoma or a benign naevus, so that subtypes present as new or changing lesions may inform advice this information is not always reliable.16 Indeed, it has on how to detect these melanoma subtypes at their earliest been reported that about one-third of patients without histo- presentation. Our secondary aim was to investigate the associ- j logical evidence of a naevus erroneously recall a pre-existing 16 October 2017 ation between naevus-associated melanoma and other clinical naevus.18 and pathological characteristics, allowing us to determine A correlation between various clinical and pathological charac- whether there are any confounders of the potential relationship teristics and naevus-associated and de novo melanoma has been between naevus association and superficial spreading and reported in several studies.6,9,12,14-17,19 Earlier studies have nodular melanoma subtypes. 1 Victorian Melanoma Service, Alfred Hospital, Melbourne, VIC. 2 Monash University, Melbourne, VIC. 3 Alfred Health, Melbourne, VIC. * Equal first authors. 333 [email protected] j doi: 10.5694/mja17.00232 j See Editorial, p. 330 Research fi 1 Nodular melanoma with ve dermal and subcutaneous 3 Clinical and pathological characteristics of satellite deposits. Breslow thickness, 6.4 mm, Clark level IV naevus-associated and de novo melanoma (invasion into the reticular dermis), ulcerated with seven mitoses; arose de novo on the left posterior lower leg of Naevus- Characteristic All associated De novo P a 66-year-old man All melanomas 3678 1360 (37.0%) 2318 (63.0%) Histological subtype < 0.001 Superficial 3057 1289 (42.2%) 1768 (57.8%) spreading Nodular 621 71 (11%) 550 (88.6%) Amelanosis/hypomelanosis < 0.001 Yes 283 45 (16%) 238 (84.1%) No 3395 1315 (38.7%) 2080 (61.3%) Breslow thickness < 0.001 1.0 mm 1997 964 (48.3%) 1033 (51.7%) 1.01e4.0 mm 1357 357 (26.3%) 1000 (73.7%) > 4.0 mm 279 36 (13%) 243 (87.1%) Sex 0.29 Men 1943 735 (37.8%) 1208 (62.2%) Women 1735 625 (36.0%) 1110 (64.0%) Anatomic location < 0.001 Head and neck 485 111 (22.9%) 374 (77.1%) 2 Superficial spreading melanoma. Breslow thickness, 1 mm, Upper extremities 799 265 (33.2%) 534 (66.8%) Clark level IV, non-ulcerated with one mitosis; arose within a pre-existing naevus on the left lower back Lower extremities 968 283 (29.2%) 685 (70.8%) of a 39-year-old man Trunk 1395 688 (49.3%) 707 (50.7%) Age group < 0.001 < 30 years 253 137 (54.2%) 116 (45.8%) 30e49 years 1213 545 (44.9%) 668 (55.1%) 50e69 years 1488 516 (34.7%) 972 (65.3%) 70 years 709 158 (22.3%) 551 (77.7%) Fitzpatrick skin type* 0.46 I 1020 362 (35.5%) 658 (64.5%) II 1549 580 (37.4%) 969 (62.6%) III/IV 1008 383 (38.0%) 625 (62.0%) Personal history of melanoma 0.04 Yes 518 210 (40.5%) 308 (59.5%) No 3013 1077 (35.7%) 1936 (64.3%) Family history of melanoma 0.17 Yes 827 323 (39.1%) 504 (60.9%) Methods No 2843 1035 (36.4%) 1808 (63.6%) The Victorian Melanoma Service (VMS) is a statewide, multidis- *I¼ always burns, never tans; II ¼ burns easily, tans poorly; III ¼ burns moderately, ciplinary tertiary referral service based at the Alfred Hospital in then develops a light tan; IV ¼ burns minimally to rarely, then develops a moderate tan; V ¼ rarely burns, tans darkly easily; VI ¼ never burns, always tans darkly. u Melbourne; it reviews about one-quarter of new melanoma cases in Victoria. The VMS database includes data on all patients treated at the service. Data for all patients with nodular melanomas and study if information on the presence or absence of an associated superficial spreading melanomas diagnosed at the VMS during naevus was not recorded. 1994e2015 were included in this study. 16 October 2017 The anatomic location of the primary tumour was categorised into j An expert VMS dermatopathologist provided histopathological the following groups: head and neck, trunk, and extremities. review of each melanoma. Tumour histological subtype was clas- Patient-related variables were recorded by the treating doctor sified according to the World Health Organization classification during the patients’ initial presentation. system as superficial spreading melanoma, nodular melanoma, MJA 207 (8) lentigo maligna melanoma, acral lentiginous melanoma, or des- Clinical and pathological characteristics extracted from the data- moplastic melanoma. Our study assessed only the superficial base included age, sex, Fitzpatrick skin type, personal history of spreading and nodular melanoma subtypes. The histopathological melanoma, family history of melanoma, anatomic location of the 334 review recorded the presence or absence of an associated naevus primary tumour, Breslow thickness, histological subtype and for each melanoma. Data for patients were excluded from our amelanosis/hypomelanosis as assessed by the patient and family. Research Ethics approval 4 Univariable and multivariable logistic regression analysis of the Institutional ethics approval to conduct